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AAV-mediated conversion of human pluripotent stem cell-derived pacemaker.
Chan, Patrick K W; Geng, Lin; Gao, Yi; Keung, Wendy; Li, Ronald A.
Affiliation
  • Chan PKW; Ming Wai Lau Centre for Reparative Medicine, Karolinska Institutet, Stockholm 17177, Sweden.
  • Geng L; Dr. Li Dak-Sum Research Centre, The University of Hong Kong-Karolinska Institutet Collaboration in Regenerative Medicine, The University of Hong Kong, Pokfulam, Hong Kong.
  • Gao Y; Dr. Li Dak-Sum Research Centre, The University of Hong Kong-Karolinska Institutet Collaboration in Regenerative Medicine, The University of Hong Kong, Pokfulam, Hong Kong.
  • Keung W; Dr. Li Dak-Sum Research Centre, The University of Hong Kong-Karolinska Institutet Collaboration in Regenerative Medicine, The University of Hong Kong, Pokfulam, Hong Kong.
  • Li RA; Ming Wai Lau Centre for Reparative Medicine, Karolinska Institutet, Stockholm 17177, Sweden; Dr. Li Dak-Sum Research Centre, The University of Hong Kong-Karolinska Institutet Collaboration in Regenerative Medicine, The University of Hong Kong, Pokfulam, Hong Kong. Electronic address: ronald.li@ki.se
Biochem Biophys Res Commun ; 494(1-2): 346-351, 2017 12 09.
Article in En | MEDLINE | ID: mdl-28989025
ABSTRACT
Malfunction of nodal pacemaker (Pm) cardiomyocytes (CMs) due to diseases or aging leads to rhythm generation disorders, necessitating electronic Pm implantation. We functionally reprogrammed human pluripotent stem cell (hPSC) derived-ventricular (V) CMs into -PmCMs via recombinant adeno-associated virus serotype 9 (rAAV9)-mediated overexpression of engineered HCN1 channel (HCN1ΔΔΔ) whose S3-S4 linker has been strategically deleted by design to promote cardiac pacemaking. rAAV9-HCN1ΔΔΔ-reprogrammed hPSC-PmCMs converted from -VCMs showed automaticity and action potential parameters typical of native nodal PmCMs. Implantation of rAAV9-HCN1ΔΔΔ-based BPm in a preclinical porcine model of complete heart block significantly reduced the dependence on device-supported pacing and generated spontaneous heart rhythms from the BPm. Collectively, these results have further laid the groundwork on BPm for future translation.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Potassium Channels / Dependovirus / Myocytes, Cardiac / Pluripotent Stem Cells / Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels / Heart Block / Heart Ventricles Limits: Animals / Humans Language: En Journal: Biochem Biophys Res Commun Year: 2017 Document type: Article Affiliation country: Suecia
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Potassium Channels / Dependovirus / Myocytes, Cardiac / Pluripotent Stem Cells / Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels / Heart Block / Heart Ventricles Limits: Animals / Humans Language: En Journal: Biochem Biophys Res Commun Year: 2017 Document type: Article Affiliation country: Suecia